A rational basis for mucosal vaccination against HIV infection.

The lack of success in the development of an effective conventional vaccine against HIV has focused attention on mucosal immunity. This is a rational move, since HIV is transmitted mostly by the mucosal route. The mucosal strategy is based on the concept that: a) HIV/SIV has to cross the mucosal-regional lymph node-blood barriers, each of which can prevent viral transmission or decrease the viral load. b) Immunization has to target directly the mucosal tissues or indirectly the regional lymph nodes, in order to prevent or control viral replication. This strategy is consistent with antigen localization and effective entry into the lymph nodes, driving the immune response. c) A dual immune mechanism may be necessary for effective mucosal protection, mediated by specific CD4 and CD8 T-cell and antibody responses to the immunizing antigens, and innate antiviral factors and beta-chemokines which down-modulate CCR5 co-receptors. Targeted iliac lymph node immunization with SIVgp120 and p27 in alum prevents SIV infection or significantly decreases the viral load when challenged by the rectal route. Indeed, in addition to specific immunity, including significant sIgA antibody-forming cells in the iliac lymph nodes, CD8-suppressor factor and the three beta-chemokines (RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta) are significantly associated with protection against rectal mucosal SIV infection.